6. PROJECT 2. ANALYZING AND ENGINEERING NETWORKS THAT CONTROL SPATIAL ORGANIZATION SUMMARY The goal of this project is to understand the logic of spatial decision-making in biological systems. A hallmark of living systems is their ability to form complex structures that are essential for their function. Remarkably, such biological structure, both at the intracellular level as well as the multicellular level, arise through a process of self-organization; the individual components (molecules or cells) function as a collective system to create global order from the bottom-up, despite the fact that these components are distributed and can generally only execute simple local regulatory rules. How self-organizing principles dynamically shape the spatial organization of the cell and multicellular structures remains a fundamental yet poorly understood question in cell biology. Ultimately, if we could understand how to engineer spatial self-organizing systems, this would have important implications in controlling cellular shape, movement, and function or in the engineering of complex multicellular structures, such as organs. Here we focus on a set of example intracellular and multicellular spatial behaviors and propose to identify and characterize the core self-organizational algorithms that can yield these behaviors using a combination of systematic perturbation, computational analysis, and synthetic reconstitution. LEAD Investigator: MARSHALL Investigators: MARSHALL, GARTNER, THOMSON, LIM, MOSTOV, ALTSCHULER, WU